Critical Insights into Untargeted GC-HRMS Analysis: Exploring Volatile Organic Compounds in Italian Ambient Air

This study critically examines the workflow for untargeted analysis of volatile organic compounds (VOCs) in ambient air, from sampling strategies to data interpretation by using GC-HRMS. While untargeted approaches are well-established in liquid chromatography (LC) due to advanced-deconvolution tools and extensive metabolomic libraries, their application in gas chromatography (GC) remains less developed, particularly for VOCs. The high structural isomerism of VOCs and the relative novelty of GC-based untargeted methodologies present unique challenges, including limited software tools and reference libraries. Air samples from suburban and rural sites in central Italy were analyzed to explore chemical diversity and address methodological gaps. This study evaluates critical decisions, such as sampling strategies, extraction techniques, and data-processing workflows, highlighting the limitations of automated deconvolution tools and the need for manual validation. Results revealed distinct source contributions, with suburban areas showing higher levels of anthropogenic compounds and rural areas dominated by biogenic emissions. This work underscores the potential of GC-HRMS untargeted analysis to advance environmental chemistry, while addressing key pitfalls and providing practical recommendations for reliable application. By bridging methodological gaps, it offers a roadmap for future studies aiming to integrate untargeted and targeted approaches in air quality research.